重组人脑利钠肽对大鼠心肌梗死后心室重构及功能的影响

Effects of rhBNP on left ventricular remodeling in rats with acute myocardial infarction

目的探讨重组人脑利钠肽（rhBNP）对心肌梗死后大鼠心室重构及心功能的影响。方法建立急性心肌梗死（AMI）雄性SD大鼠模型45只，随机分为AMI对照组、小剂量rhBNP治疗组、大剂量rhBNP治疗组，每组各15只。另设15只作假手术组。rhBNP治疗组经颈静脉输液管输注rhBNP，剂量分别为5μg／kg和15μg/kg，1次／d，持续4周，假手术组及AMI对照组仅以等体积的生理盐水输注。4周后检测血液动力学及心功能参数，心脏标本检测左室重量及左室重量指数（LVMI）、心肌梗死面积，并检测血浆和心肌血管紧张素Ⅱ（AngⅡ）水平。结果AMI对照组左室重量、LVMI及心肌AngⅡ水平明显高于假手术组，而收缩压及左室内压最大上升和下降速率（±dp／dt）均明显低于假手术组（均P〈0．01）。大、小剂量rhBNP治疗组左室重量及LVMI、心肌梗死面积和心肌AngⅡ水平均明显低于AMI对照组[左室重量：分别为（492．6±34.0）mg、（498．8±47．8）mg比（570．0±24．2）mg，P〈0．01；LVMI：2．0±0．2、2．0±0．2比2．3±0．1，P〈0．01；心肌梗死面积：（25．3±2．9）％、（31．4±3．0）％比（46．4±3．0）％，P〈0．01；AngⅡ水平：（881．3±62．7）pg／L、（1186．0±94．5）pg／L比（2436．7±280．3）pg／L，P〈0．05]，收缩压和±dp／dt也高于AMI对照组（P〈0．01或P〈0．05）。结论外源性的rhBNP连续应用能限制梗死面积、减轻AMI后心室重构、保护心功能。

Objective To assess the effects of rhBNP on left ventricular （LV） remodeling in rats with acute myocardial infarction （ AMI ）. Methods AMI was induced by ligating coronary arteryin male Sprague Dawley rats. Two days after surgery, AMI rats received intravenous infusion of rhBNP （ 15 μg/kg or 5 μg/kg once daily, n = 15 each） or saline （placebo control, n = 15 ） through Jugular Vein. Sham-operated rats （n = 15 ） served as normal control. Four weeks later, hemodynamic measurements were performed, left ventricular weight （ LVW）, ratio of left ventricular weight to body weight （ LVW/BW）, left ventricular diameter （LVD） and infarct size were determined. Plasma angiotensin Ⅱ and myocardial angiotensin Ⅱ levels were also measured. Results Compared with sham-operated rats, LVW, LVW/BW, LVD and myocardial angiotensin Ⅱ level were significantly increased, while the LV systolic pressure （LVSP） , ± dp/dt were significantly reduced in saline treated AMI rats （ all P 〈 0. 05 ） . LVW/BW, MI size, LVD and myocardial angiotensin Ⅱ in rhBNP treated AMI rats were significantly lower [ LVW： （492. 6 ± 34. 0）mg, （498.8±47.8）mg, （570.0±24.2）mg,P〈0.01; LVW/BW： 2.0 ±0.2, 2.0±0.2, 2.3 ±0.1,P〈 0. 01 ; LVD ： （ 25.3 ± 2. 9 ） %, （ 31.4 ± 3.0 ） %, （ 46.4 ± 3.0 ） %, P 〈 0. 01 ; myocardial angiotensin Ⅱ ： （881.3 ±62. 7） pg/L, （1186. 0 ±94. 5） pg/L, （2436. 7 ±280. 3） pg/L, P〈0. 05], while LVSP and ± dp/dt in rhBNP treatment groups were significantly increased than saline treated AMI rats （ P 〈 0. 05 or P 〈 0. 01 ）. Conclusion RhBNP is effective in attenuating left ventricular remodeling after AMI in rats.